Head injury is still a major cause of death and disability despite the implementation of aggressive methods of evaluation and intensive care. It is our feeling that if further gains are to be made in improving patient outcome, new efforts must be directed at the basic pathophysiologic processes involved in severe head injury. Based upon extensive data obtained in our laboratories, we have chosen to target our therapeutic efforts at the damaging consequences of oxygen radicals on the cerebral vasculature. Specifically, the hypothesis is that the action of free radicals on the cerebral vasculature contributes significantly to the morbidity and mortality of severe head injury, and quenching of free radicals with PEG-SOD* can improve the outcome in patients with severe head injury. To prove this hypothesis, we will conduct a prospective, randomized, double-blind, Phase III trial. The patients will be divided for the Phase III trial into 2 groups: (1) a control group, and (2) a group treated with PEG-SOD. The efficacy of this agent will be measured by the Glasgow Outcome Score (GOS) at one year, as well as by other measures of outcome, specifically the Disability Rating Scale (DRS) and the Los Ranchos Amigos Outcome Scale. Other measures of efficacy will also be used; these include dynamic intracranial pressure (ICP) monitoring coupled with measurements of vascular reactivity, the neurologic exam, and biochemical assays of appropriate products of lipid peroxidation.